Indoleamine 2,3-Dioxygenase (IDO) Expression in Invasive Breast Carcinoma (IBC) Is Associated with Longer Relapse-Free Survival (RFS)
MR Steciuk, JD Pfeifer, MA Watson, O Hameed. University of Alabama at Birmingham, Birmingham, AL; Washington University, St. Louis, MO
Background: Mechanisms of immune evasion are emerging as critical factors in tumor progression. The enzyme IDO catabolizes tryptophan, depleting it from the tumor microenvironment, thus preventing T-cell activation, and facilitating immune evasion. IDO is overexpressed in many human cancers, sometimes associated with poor prognosis. We report results of a tissue microarray (TMA) analysis of IDO expression in IBC.
Design: Clinical findings, follow up data (obtained from the tumor registry), and pathological data (from pathology reports and slide review) for 439 patients with IBC diagnosed between 1992 and 1998 were reviewed. Formalin-fixed paraffin-embedded tissues were plated to a TMA. The TMA was stained by IHC for ER, PR, HER2, Ki-67 as well as for IDO. The latter was semi-quantitatively scored on a 0-4+ scale and compared with clinical data and expression of markers listed above.
Results: IDO was expressed in 273 (95.8%) of 285 IBCs at 1+ or above. Preliminary analysis showed that IDO expression did not correlate with age, overall survival, tumor size, grade, nodal status, lymphocyte infiltration, or expression of ER, PR, HER2, or Ki-67. Surprisingly, IDO expression correlated with longer RFS (r=0.269; p=0.047). Kaplan Meier curves indicated this may be due to IDO-negative tumors having greater rates of early relapse (see figure). Indeed, IDO-negative tumors had shorter RFS than IDO-positive tumors (5.0 vs 27.6 months; p=0.001) despite that IDO-positive tumors had more positive lymph nodes than IDO-negative tumors (4.3 vs 1.0; p=0.002). When other cutoffs were considered as IDO-negative (0, 1+) or positive (2+, 3+, 4+), IDO expression did not predict ER or PR expression, but IDO-positive tumors were more frequently HER2-positive than IDO-negative tumors (9.8% vs. 1.7%; p=0.048) and more likely to have a pure lobular phenotype (12.2% vs 2.8%, respectively; p=0.021).
Conclusions: IDO is widely expressed in IBCs and is associated with longer RFS, HER2 expression, and lobular phenotype. Further study is necessary to replicate these findings and elucidate their significance.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 51, Monday Morning